Toilet preparation



Patented June 1, 1943 TOILET PREPARATION George Sperti, Cincinnati, Ohio, assignor to The Institutum Divi Thomae Foundation, Cincinnati, Ohio, a corporation of Ohio No Drawing.

Application June 19, 1939,

Serial No. 279,998

10 Claims.

This invention relates to cosmetic or detergent preparations intended for external or topical application, and more particularly to the efiect of such preparations on the respiration of the tissues to which they are applied. The field of application of the invention thus includes toilet preparations, such as lotions, creams, oils, and detergents, such as toilet soaps, mouth washes and tooth pastes, etc., all of which are to be understood as included within the terms cosmetics and detergents as employed herein and in the appended claims. This application is a continuation in part of my prior application Serial No. 184,338, filed January 10, 1938.

It is known that human skin respires, taking up oxygen from the surrounding atmosphere and from the blood stream apparently as a function of the cell life in the skin tissue. It is furthermore known that one difierence between old skin and young skin is that the rate of respiration declines with age, young skin respiring or breathing more rapidly than old skin and absorbing greater quantities of oxygen. Moreover, it appears that skin which has not been exposed to some stimulatinginfiuence, such as light, wind, massage, etc, shows depressed respiration.

Heretofore, as far as I am aware, no practicable way has been devised to stimulate skin respiration by the application of cosmetics. In fact, it has been found that all cosmetics and detergents tested, although they may possess other beneficial properties. have the undesirable action of depressing tissue respiration, thus exaggerating the normal decline in respiration which takes place with increasing age as well as the depressed respiration existing under ordinary conditions. For a study of this nature, it is desirable in order to obtain scientific determinations of respiration to measure oxygen consumption of the tissues by suitable manometric methods, such as disclosed for example in the standard work Manometric Methods by Malcolm Dixon; the so-called direct method of Warburg is well adapted for such measurements.

Two procedures are available: (1) in vitro experiments in which the substance tested is added to the skin fragments in the manometer flask; (2) topical application experiments in which the cosmetic is applied to the skin for a given period, any excess of cosmetic being removed before excision of the skin. Both types of experiments are controlled with normal untreated skin from the same animal or person, and, in the second case, the control skin is rubbed the same length of time as the experimental to eliminate stimulation due to massage. While the first method will reveal acute toxic manifestations, the second method more nearly reproduces the conditions found in practice. De-

pression is encountered by both methods, as shown by the examples given below. Creams are usually less active depressants than are soaps and lotions. These depressant efiects of cosmetics may be attributed to a number of causes each of which is probably operative to a variable degree. Among them are the previously demonstrated adverse effects of antiseptics, fatty acids, and unphysiological pH.

As disclosed in my copending application Serial No. 280,000, filed June 19, 1939 concurrently herewith, it has been found that agents having the property of stimulating tissue respiration can be produced in a number of ways, and as illustrated by the examples below, the addition of such stimulating agents in suitable amounts to cosmetics and detergents has the efiect of counteracting the usual depressant effects thereof. While the particular source of and procedure for obtaining such respiratory stimulating agents is not a part of the present invention, suitable illustrative procedures are given by way of example.

Example 1 Yeast is a convenient source of material which can readily be processed and which provides a substantial yield of the respiratory stimulating substances. The following procedure may be followed for producing the crude preparation.

Seven pounds of fresh Fleischmanns bakers yeast were extracted with 2.5 liters of 95% ethyl alcohol for four hours at a temperature of 60-'70 C. with constant mechanical stirring. The alcohol lost during the extraction was continually replaced. The mixture was then filtered. through a Biichner funnel and the residue reextracted with 2.5 liters of 50% ethyl alcohol under the same conditions. The extracts were filtered until clear and the residues discarded. The combined filtrates contained a crude respiratory stimulating substance which was obtained in solid form by evaporating the combined filtrates to 400 cc. under reduced pressure at a temperature not greater than 60 C. and then evaporating the extract to dryness at 70 C. This crude substance when tested for its capacity to stimulate cellular respiration according to the manometric methods referred to above, showed stimulation with respect to both rat skin and human skin.

The crude extract described above is suitable for use in some cases, as in soap, but may have an objectionable odor or color when used in other preparations, such as face creams, mouth washes, etc. For such purposes it is therefore desirable to refine the crude extract. This extract is substantially free of protein but contains small amounts of certain dissolved protein substances which it is first desirable to remove. This may readily be accomplished by precipitation with a suitable precipitating agent, barium hydroxide being well suited because excess barium can readily be removed. The following procedure is illustrative: To 200 cc. of the extract were slowly added with constant stirring 800 cc. of a hot saturated solution of barium hydroxide. A volume of 95% ethyl alcohol, equal to twice the volume of the extract plus the barium hydroxide, was then added with constant stirring which was conparts to decolorize at'5-8 C. (sample 1), room temperature, which was about C. (sample 2), and 60 C. (sample 3). The solution was either heated or cooled to the proper temperature and approximately one-tenth its weight of charcoal added. After stirring well for a few minutes, the material was filtered through a Biichner funnel. The charcoal was thenremoved from the filter,

. stirred in the same solvent at the same temperatinued for ten minutes after the addition had of 150 cc. at -55 C. and was filtered through a Biichner funnel to remove the barium carbonate precipitate. The filtrate was then warmed to 60 C. on a water bath and 2.5 N. sulphuric acid was added slowly with constant stirring until all the barium was precipitated, 22 cc. of acid being required. The barium sulphate was filtered out, leaving a perfectly clear filtrate which was evaporated to dryness at 70 C. This material showed definite stimulation of respiration on skin of the order of -65%.

For further refinement of the filtrate described immediately above, this filtrate was treated with acetone by adding three liters of acetone slowly, with shaking, to 150 cc. thereof, allowing the mixture to stand at room temperature for seventytwo hours, after which the acetone solution was decanted from the red oily precipitate, This precipitate, after washing with acetone and dry ing at 70 C. showed marked stimulation on skin.

A similar productwas also obtained from the precipitate from the original barium hydroxide precipitation. To remove. the water soluble constituents, this precipitate was stirred with a 100 cc. portion of distilled water at room temperature and filtered. After this operation had been repeated three times, the combined washings were saturated with carbon dioxide, the solution reduced in vacuum at 40 C. to a volume of 54 cc., and the barium carbonate filtered off and discarded. The clear, reddish filtrate was then heated to 60 C. and 2 cc. of 2.5 N. sulphuric acid were slowly added with stirring, after which the barium sulphate formed was allowed to settle and filtered off. The solution was evaporated to dryness at 70 C. and the resulting product showed definite stimulation of skin respiration.

Example 2 A simpler method of refining the crude alcoholic yeast extract described in the foregoing example is by the use of an adsorbent, such as charcoal, diatomaceous earth, etc., as a refining agent. The above described method of extracting Fleischmanns bakers yeast with 95% ethyl-alcohol and then with ethyl alcoholv and then combining and concentrating the extracts may be followed to obtain the crude extract. The following procedure illustrates the refinement of this crude extract by means of activated char-. coal.

The concentrate was divided into three portions and dried in the oven at 50-55 C. The dry material was dissolved in distilled water (sample A). 25 per cent ethyl alcohol (sample B) and 40 per cent ethyl alcohol- (sample C) .to a concentration of approximately 50 mg. per cc. The three solutions were then further divided into 3 ture as the previous treatment, and again filtered to remove adhering material, and the washings were added to the original filtrate. 1

The original crude, after drying and making up to the proper concentration with the various solvents, was dark brown in color and had an objectionable yeast-like odor. After treatment with the charcoal, in every case, the color became lighter and the odor less disagreeable. The water decolorizations were more eflective in removing the color and odor than the alcoholic ones, and the 5-8 C. and 60 C. treatments. were better than. the room temperature decolorizations. Two or three successive treatments of this water solution at 60 C. gave water-white and nearly odorless preparations.

For testing the dried samples were made up to a concentration of 50 mg. per cc. or, if the quantity of material was small, as in the case of the charcoal adsorbed material, as high a concentration as possible was used. The pH was determined by the glass electrode and adjusted to 7.3 with sodium hydroxide or hydrochloric acid for testing on yeast and skin respiration. If the pH of the samples was between 5.6 and 7.3 they were sterilized at 15 pounds pressure for 15 minutes before adjusting the pH. It had been found earlier that the respiratory stimulating factors may be sterilized within this pH range without loss of activity. Samples, the initial pH of which lay outside the above range, were adjusted to pH 7.3 before sterilization.

The decolorized filtrates were tested on skin by the manometric method referred to above. While all of the samples showed stimulation oi skin respiration, those giving the best. results were as follows:

Ten pounds of fresh beef spleens were skinned,

cut into small pieces and washed with cold water to remove blood. The pieces were ground in a meat grinder and extracted with 4 liters of distilled water for one hour at 45 C. with constant mechanical stirring. The material was filtered through cheesecloth and muslin and squeezed as dry as possible. To 3 liters of this filtrate was added 12 liters of 95% ethyl alcohol to give a final alcohol concentration of This caused the formation of a precipitate which was filtered off on a Biichner funnel and was then extracted with 1.5 liters of water. Th material was then filtered on a Biichner funnel and the filtrate was concentrated to small volume in vacuo at not greaterthan 65 C. and brought to dryness in an oven at 50 C. In manometer tests this material showed stimulation of skin respiration of 42%.

Respiratory stimulating agents as above described are oluble in water and dilute alcohol and stable to heat and in the presence of alkalis and moderately strong acids. Hence they are well adapted for use in cosmetics and detergents, although it will be understood that within the broad aspect of the invention any other suitable respiratory stimulating agent may be substituted therefor. The amount to be used depends somewhat on the potency of the specimen used, but is primarily controlled by the extent to which stimulation is desired in a cosmetic preparation for general distribution and also on the extent of the depressing action of the preparation in which it is used.

Examples of typical cosmetic and detergent preparations containing a respiratory stimulating agent (R. S. R). It will be understood that the amount of R. S. F. used in these examples is illustrative only and that either more or less may be used depending on the effect desired in any particular case.

Example 4.Vanishing cream Grams Stearic acid 180 Caustic soda 9 Glycerine 50 Water (distilled) 750 Perfume 11 R. S. F 10 Example 5.C'old cream Grams Liquid parafiin 300 Solf. white paraflin 200 White beeswax 100 Stearic acid 14 Triethanolamine 6 Borax 10 Water (distilled) 300 Perfume R. S. F

Example 6.Soap

Grams Soap stock 920 Sodium hydroxide 120 R. S. F 10 Perfume Water 150 Example 7.Emollient skin balm Gum karaya g 3.5 Water (distilled) cc 108.6 Glycerine cc 18.9 95% alcohol cc 76.1 Salicyclic acid --g 0.1944 Carbolic acid g .3240 Powdered soap g 3.0 R. S. F g 2.10

Perfume Example 8.Skin fresheners Grams Alum Borax 30 Glycerine 30 Alcohol 200 Orang flower water 300 Rose water 400 R. S. F 10 The addition of the respiratory stimulating agent may be made in any suitable manner according to the nature of the preparation. For example, the agent may be dissolved in a small quantity'of a suitable solvent such as dilute alcohol or water and then mixed with a skin cream, lotion, soap, etc., the solvent being thereafter evaporated off if desired. These methods are only illustrative, however, and can be varied to suit manufacturing procedures and conditions in any particular case.

Carefully controlled manometer tests have demonstrated that these cosmetic preparations (creams, lotions and toilet soaps) containing the respiratory stimulating agent do increase skin respiration as compared with the same cosmetics without any such agent. Thus the use of this agent in cosmetics in whole or in part prevents the respiration of the skin, which is depressed under the usual living conditions, from further depression by use of the cosmetics, as shown by the following examples:

Example 9.Topz'cal application of lotion to human skin Three areas of skin in the same region were selected on a patient twenty to thirty years of age. One area (control) was rubbed with Ringer solution. The second area was rubbed with a mixture of Ringer solution and a coimnercial 10- tion, and the third was rubbed with a mixture of Ringer solution containing 39.4 mg. per cc. of an R. S. F. preparation and the same amount of 10- tion. The skin areas were then removed and tested for respiration in the manometer.

The results of the experiments are as Lollows:

, Averz age A \vrtotal age For Flask Time weight )2 con- Q01 cent dem sumed in on. crease .grmns 2 2;?

Ilours Control-Rin zor only 2 .0025 (5.31 1.262 Experimentallotion plus Ringer 2 .0018!) 1.x) .488 (ii Experimentallotion plus Ringer plus R. S F 2 (102i 3. l2 T72 39 It will be seen that in this experiment enough R. S. F. was added to partially overcome the depressing action of the lotion.

Example 10.---Topical application of soap to human skin 0 In this experiment sufiicient R. S. F. was added to overcome about two-thirds of the depressing action of the soap.

Example 11.-Tpical application of facial cream to human skin Three areas of skin in the same region were selected on a patient twenty to thirty years old. One area (control) was rubbed with Ringer solution. The second was rubbed with a mixture of facial cream and Ringer solution, and the third with a mixture of Ringer solution, containing 39.4 mg. per cc. of an R. S. F. preparation and the same amount of cream. The skin areas were then removedand tested in the manometer.

The results are given in the following table:

Averg age A vcrdry total age For Flask 'Iimc Wei ht 02 con- Q0: cent don? s umed in cu. crcasc grams 1111i1 mm.

. Hours Control-Ringer only". 2 0020 9. 47 2. 366 E xperimental-crcam plus Ringer; 2 .0014 5. 96 2.117 6 Experimental-cream plus Ringer plus R. S. F 2 0017 8. 09 2. 361 0. 3

In this experiment the addition of R. S. F. completely overcame the depressing action of the cream.

' It will be understood that changes may be made in the procedures, proportions, and other details set forth above, and that respiratory stimulating agents may be obtained from other sources and by other methods than those particularly described. These particulars are set forth herein by way of illustration only and many such changes will now suggest themselves to those skilled in the art without departure from the spirit of the invention. Hence reference should be had to the appended claims to define the limits of the invention.

What is claimed is:

1. A toilet preparation for topical application comprising a. preparation which depresses the respiration ofthe tissue to which it is applied combined with a respiratory stimulating agent which stimulates the tissue respiration as determined by-manometric measurements and thereby compensates at least in part for the depressing eiT'ect of said preparation.

2. A toilet preparation for topical application comprising a respiratory stimulant capable of stimulating the respiration of tissue to which it isapplied as determined by manometric methods combined with a saponaceous agent inert to said as determined by manometric measurement, the soap being compatible with said respiratory stimulating factor to retain and make available its respiration stimulating properties upon use of said soap.

5. A new composition of matter for topical application for cosmetic purposes comprising a skin cream which depresses tissue respiration having incorporated therein a respiratory stimulating factor capable of stimulating tissue respiration as determined-by manometric measurement, the skin cream being compatible with said respiratory stimulating factor to retainand make available its respiration stimulating properties upon use of said skin cream.

6. A new composition of matter for topical application for cosmetic purposes comprising a lotion which depresses tissue respiration having incorporated therein a. respiratory stimulating factor capable of stimulating tissue respiration as determined by manometric measurement, the lotion being compatible with said respiratory stimulating factor to retain and make available its respiration stimulating properties upon use of said lotion. 4

7. A new composition of matter for topical application'for cosmetic purposes comprising a cosmetic which depresses tissue respiration having incorporated therein a respiratory stimulating factor capable of stimulating tissue respiration as determined by manometric measurement, the cosmetic being compatible with said respiratory stimulating factor to retain and make available its respiration stimulating properties upon use of said cosmetic, said respiratory stimulating factor comprising the concentrated water-soluble constituents of cellular matter.

8. A new composition of matter for topical application for cosmetic purposes comprising a cosmetic which depresses tissue respiration having incorporated therein a respiratory stimulating factor capable of stimulating tissue respiration as determined by'manometric measurement, the cosmetic being compatible with said respiratory stimulating factor to retain and make available its respiration stimulating properties upon use of said cosmetic, said respiratory stimulating factor comprisingthe concentrated water-soluble constituents of yeast cells. I i

9. A new composition of vmatter for topical application for cosmeticpurposes comprising a cosmetic which depresses tissue respiration having incorporated therein a respiratory stimulating factor capable of stimulating tissue respira-. tion as determined by manometric measurement, the cosmetic being compatible with said respiratory stimulating factor to retain and make available its respiration stimulatingproperties upon use of said cosmetic, said respiratory stimulating factor comprising the acetone-insoluble portion of the water-soluble constituents of cellular matter.

10. A new composition of matter for topical application for cosmetic purposes comprising a. cosmetic which depresses tissue respiration having incorporated therein a. respiratory stimulating factor capable of stimulating tissue respiration as determined by manometric measurement, the cosmetic being compatible with said respiratory stimulating factor to retain and make available its respiration stimulating properties upon use oi. said 'co'smetic, said respiratory stimulating factor comprising the-acetone-insoluble portion of the water-soluble constituents of yeast cells.

GEORGE SPERTL 

